Abstract
Respiratory diseases adversely affect infants and are the focus of efforts to develop vaccinations and other modalities to prevent disease. The infant immune system differs from that of older children and adults in many ways that are as yet ill understood. We have used a C57BL/6 mouse model of infection with a laboratory- adapted strain of influenza (PR8) to delineate the importance of the cytokine IL-6 in the innate response to primary infection and in the development of protective immunity in adult mice. Herein, we used this same model in infant (14 days of age) mice to determine the effect of IL-6 deficiency. Infant wild type mice are more susceptible than older mice to infection, similar to the findings in humans. IL-6 is expressed in the lung in the early response to PR8 infection. While intramuscular immunization does not protect against lethal challenge, intranasal administration of heat inactivated virus is protective and correlates with expression of IL-6 in the lung, activation of lung CD8 cells, and development of an influenza-specific antibody response. In IL-6 deficient mice, this response is abrogated, and deficient mice are not protected against lethal challenge. These studies support the importance of the role of the tissue environment in infant immunity, and further suggest that IL-6 may be helpful in the generation of protective immune responses in infants.
Highlights
Respiratory tract inflammatory and infectious disease in infant children represents a significant burden to the healthcare system [1, 2]
Several lines of evidence suggest that children less than five years of age are more susceptible to seasonal influenza virus infection [3, 49] and this led us to first investigate the age-related susceptibility of infant mice to influenza
Since the basal levels of Interleukin 6 (IL-6) gene expression in lung epithelial cells in infants was significantly lower when compared to adults, we examined whether i.n. administration of the inactive influenza virus vaccine could upregulate IL-6 expression
Summary
Respiratory tract inflammatory and infectious disease in infant children represents a significant burden to the healthcare system [1, 2]. Alternative models suggest that T cells in neonates/infants are not inherently tolerant, but that tissue specific signals can affect T cell activation and effector function by limiting or supporting the access to productive antigenic signals [9,10,11,12,13,14,15,16,17]. For influenza virus and other respiratory infections, the epithelium of the respiratory tract provides a unique environment that can tune adaptive immune responses. The potential effect of lung epithelial cells in the immune responses of infants is a recent area of inquiry, and could be a significant determining factor in their apparent altered immune response during influenza virus infection
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